Supernumerary Der(22)t(8

A number sign (#) is used with this entry because of evidence that this phenotype is caused by malsegregation of a t(8;22)(q24.13;q11.2) translocation, one of only a few recurrent non-Robertsonian constitutional translocations in humans. See also Emanuel syndrome, 609029.

Description

Carriers of the balanced constitutional translocation t(8;22)(q24.13;q11.2) are phenotypically normal but are at risk of having progeny with supernumerary der(22)t(8;22) syndrome as a result of malsegregation of the der(22). Although the supernumerary der(22)t(8;22) phenotype is variable between individuals, it tends to include ear and extremity abnormalities in addition to mild mental retardation (summary by Sheridan et al., 2010).

Clinical Features

Sheridan et al. (2010) described 11 patients from 9 families with a syndrome characterized by extremity anomalies, mild dysmorphia, and intellectual impairment caused by 3:1 meiotic segregation of a recurrent palindrome-mediated rearrangement, t(8;22)(q24.13;q11.21). All but 1 patient had been previously reported. Two of the patients had been described by Sanchez and Yunis (1974) and 5 by Rethore et al. (1977). One child with short stature as well as the other characteristic features was described by Mark et al. (2005); 2 other patients were described by Helbig et al. (2006) and Gotter et al. (2007), respectively. Individuals with der(22) based upon this translocation had normal birth weight and growth. Moderate mental retardation was reported, with IQs ranging from 50 to 70. Dysmorphic features were prominent, low-set, and/or atretic ears often with preauricular pits. Clinodactyly was also a common feature. Several of the males had ectopic testes or cryptorchidism.

Cytogenetics

Sheridan et al. (2010) examined 10 prior reports of supernumerary der(22)t(8;22) as well as 5 prior reports of t(8;22) balanced carriers. They also described 2 new cases, a supernumerary der(22)t(8;22) carrier and his mother, a balanced translocation carrier. All nearly-identical palindromic AT-rich repeats (PATRRs) on chromosome 8 and chromosome 22 breakpoints were validated in several of the published cases as well as in the 2 of their own. PCR analysis with sperm DNA from healthy males indicated that the t(8;22) arose de novo during gametogenesis in some but not all individuals. Furthermore, demonstration that de novo PATRR8-PATRR11 translocations occur in sperm suggested that palindrome-mediated translocation is a universal mechanism producing chromosomal rearrangements. Similar to the t(11;22) translocation (see Emanuel syndrome, 609029), nondisjunction of the t(8;22) occurred during both male and female meiosis. The site-specific balanced translocation in the 9 families was paternally inherited in 3 and maternally derived in 5 (1 case was unknown). Sheridan et al. (2010) noted that the t(8;22) appears to be prone to 3:1 nondisjunction during meiosis, most likely because the der(22)t(8;22) is small, with a short interstitial segment. The only viable unbalanced t(8;22) karyotype that was observed is 47,XX or 47,XY,+der(22)t(8;22). Sheridan et al. (2010) hypothesized that this is most likely because the other unbalanced karyotypes are likely to produce almost complete monosomy 8 upon 3:1 malsegregation, and monosomy 22 or trisomy 22 upon 2:2 malsegregation.